Role of CNTNAP2 in embryonic neural stem cell regulation

CNTNAP2 is a gene that encodes a member of the neurexin family of proteins and has been implicated in autism spectrum disorders. Neurexins function in the vertebrate nervous system as cell adhesion molecules and receptors. CNTNAP2 is expressed in the region where precursor cells of the neocortex (the outer layer of the brain) originate during embryogenesis, suggesting that it has a role in regulating neural stem cells.

Nicholas Gaiano and his colleagues at Johns Hopkins University in Baltimore have conducted a series of experiments to test this hypothesis, using the developing mouse neocortex as the model system. The researchers looked at the effect of increasing or decreasing CNTNAP2 expression in the neocortex in utero. In collaboration with Daniel Geschwind’s group at the University of California, Los Angeles, they also examined the effects of deleting the CNTNAP2 gene in the mice.

The researchers’ analyses suggest that CNTNAP2 may play a subtle role in the regulation of neural stem cells of the neocortex. They did not observe a discernible change associated with high levels of CNTNAP2, although they noted altered cell migration associated with low levels of the gene. The latter is consistent with a 2011 analysis from Geschwind’s group showing that a small subset of neurons are mislocalized in the brains of mice lacking CNTNAP2.